Saturday, November 19, 2011

Handel and the Biology of Allergy, Atopy, and Suicide

With respect to classical music, I'm a much bigger fan of the classical and romantic composers (Mozart, Beethoven and all those Russian guys like Rimsky-Korsakoff) than the earlier baroque composers (such as Bach and Handel). Baroque is beautiful and often awe-inspiring, but too structured for my taste -- like a doily or a stained glass window in a church. Back then gardens were arranged into strict geometric designs. We caged nature. Then pastoralism came into vogue, and we get landscape architecture that was meant to be natural and pleasing rather than quite so civilized, and the music of the time reflects this aesthetic as well. The structure and expectations of the preceding baroque era seemed to squeeze the lyricism out of baroque music, though not the beauty.

But a baroque giant, Handel, wrote the Largo from Xerxes, a selection of music that seems to wrest poetry from rigidity. It's an amazing piece, before its time. A game-changer - who knew Handel could be passionate? According to Wikipedia, Mozart said of Handel, "[He] understands affect better than any of us. When he chooses, he strikes like a thunderbolt." Right click to open in new tab.

We have our biology, our natures. And yet we dare impose the structure of agriculture and pharmacology upon it… with an incomplete understanding, at best, particularly in the brain. Such incomplete understanding will lead seemingly learned folks to suggest that we are all diabetic. (We are not). And that glucose is not a toxin but foods that raise blood sugar levels are toxic (er, what?). I probably should not stick my foot into this one, as I am not a metabolism blogger, but for heaven's sake. Without glucose in the bloodstream we are dead. With too much glucose we are poisoned.

Physiology is all about Goldilocks, the right amounts, and the case that all starches are toxic for the vast majority of people is a very, very poor one. And if fasting glucose and overall levels of circulating glucose are important, the strict low-carber who cheats every once in a while might be in more trouble than the healthy starchy-carb eater who will be more exquisitely insulin-sensitive. As Kurt Harris and Melissa McEwen have noted, there is no evolutionary precedent for lifelong very low carb diets, and plenty of examples of healthy cultures who eat starchy carbs. So with our incomplete understanding of physiology, I feel it is a safer bet to use reasonable precedent rather than a zero-carb theory of an optimal longevity diet as a prescription for most people. Certainly there are likely exceptions - seizures, dementia, the first stage of weight loss, in many folks with diabetes. Personally I think calling starch a poison for the majority of people makes about as much sense as demonizing saturated fat.

So. Back to allergies and suicide. This part of the post is for me, really. I need a spot to look back and see the nitty gritty stuff organized in a way that makes sense to me. Actually, this is the point of the entire blog. My self-taught fellowship in Evolutionary Psychiatry.

In the beginning, there were Th1 and Th2 helper cells. These are soldiers of our immune system, called lymphocytes, with different capabilities and called into action in different circumstances. The call to war comes in the form of the release of inflammatory cytokines. There are a whole soup of these chemosignals, released also primarily by T lymphocytes, mostly named interleukins, which are shortened to IL-1, IL-2, IL-3, etc. etc.

In general - the release of inflammatory cytokines can lead to reduced activities and social interaction, and it can activate the HPA axis which can lead to supernormal responses to stress, which can further ramp up the inflammatory response. Elevated pro-inflammatory cytokines can activate the IDO enzyme, reducing serotonin production (this may explain the link between allergy and suicide). Certain types of Th2 related cytokines also increase insomnia. Allergy, then, does not increase the risk of suicide by making people feel sick, but directly through inflammatory means, leading to people withdrawing from social activities and over-react to stressful situations.

What are some more specific features? Well, proinflammatory cytokines released at the time of the allergic reaction activate the HPA axis - the glucocorticoids and catecholamines cause a suppression of Th1 and a shift to Th2 activity by inhibiting IL-12 and promoting IL-10. The pro-inflammatory cytokines also cause dysfunction of corticosteroid receptors. The Th2 lymphocyte produces IL-4, which can effect serotonin metabolism as well - and IL-4 is known to have more effect in people with some genes than others.

En anglais, we are talking here a direct mechanism by which a certain kind of stress, allergy, can affect the neurochemicals in the brain and therefore behavior, and it seems that some people are genetically more vulnerable to this stress than others. That said, other researchers have postulated that the Th1 cytokines impair the serotonin machinery even more than the Th2 ones… we're back to not too hot, not too cold, not too soft, not too hard. It all has to be just right. And what is just right? Depends on your genes and your epigenetics. Superimposing an emulation of the evolutionary milieu is only a first approximation and a good guess.

I'm really enjoying this allergy-stress-inflammation-suicide series! But I express a musical taste opposite yours. I've always been a sucker for a good baroque piece, especially Bach and Handel. I think it fits with my analytic nature, which is why I enjoy playing experimental psychologist (with its butt loads of factorial designs) so much, as well as the new fractal view of physiology (DeVany) and economics (Taleb).

I'm no music expert, but I think of at least some baroque music as more fractal, like a wild fern (such as some of the canons and fugues), than Euclidean like the geometric designs of the linked garden. I think the fractal aspect is one thing that attracted me immediately to the first baroque fugue I heard, though I didn't know what fractals were at the time.

Some links on fractal music:http://solomonsmusic.net/fracmus.htmhttp://mathtourist.blogspot.com/2008/09/fractal-in-bachs-cello-suite.htmlhttp://www.brotherstechnology.com/math/fractal-music.html

Here is an example of a fractal piece played forwards, then backwards, then in both directions at once, then with the notes in the forum of a mobius strip:http://www.youtube.com/watch?v=xUHQ2ybTejU

J - MCT oil is used for ketosis. I don't see a huge problem with it but I know it makes some people jumpy and can cause upset stomach.

Water - the paper wasn't specific. Also, some cytokines increase sleepiness… I think it's rather a mess at this point. There's a review paper I want to look at when I get a minute that may be more specific. It will likely be its own post.

LOL, if you think of fractals as not just psychedelic computer-generated images, but every complex phenomenon of nature--ferns, trees, flowers, clouds, the human heartbeat, brain neurons, galaxies, the universe--they don't seem quite as dull and nerdy. Fractals are at least not as boring as Euclidean shapes. :)

I can confirm what you said about MCT oil. Even small amounts of MCT oil definitely make me nauseas--even after trying to acclimate myself gradually over months. FWIW, I fare much better on long chain fats.

I agree with you that a ketogenic or a very LC diet shouldn't be the default diet, but I suggest to wider the area of application. Initially I went on a such diet in order to manage migraines because it was found out that my migraines were associated with an epilepsy-like activity in my brain. I was amazed to find how much ketosis improved my pre-menopausal mood. Yes, migraines are a problem, but it doesn't happens every day, however horrible mood-swings that really started to bother me after 45, were very frequent, especially 10 days before my period. Eliminating that was even more beneficial than the reduction of migraines and the shortening of their duration. Actually, during last 4 years I have no symptoms of pre-menopause at all. It is so common nowadays to hear that somebody has to treat his or her anxiety or depression with pills,or somebody's menopausal condition turns life into miserable one, that it makes me wonder, may be such people should try to calm their brains with ketogenic diet first and get a relieve, like me. Probably, slowly levering the carbo-content of the diet till the beneficial level is determent, would be even better.

The way I read it, Dr. Rosedale offered the most generalized solution. The abstraction he makes is we simply define a gradient of metabolic derangement from 0% (healthy) to 100% deranged (diabetic). His argument seems to be simply, the diet that is therapeutic for fully metabolically deranged cannot be unhealthy for the metabolically healthy.

Analogously, it's similar to most of the paleo stance on gluten grains: just because it's tolerable doesn't make it optimal.

Given that you have written about brains function on ketones, that for the same number of carbon atoms, fatty acids produce more ATP than glucose, that the body is capable of producing all the glucose it needs, Dr. Rosedale's view is by far the most generalized and better abstraction from a health perspective.

Why come up with many different models for different use cases when a single model will work? This is how evolution and natural selection does things: the best abstraction wins.

I'm not sure I can agree with Dr Rosedale's assertion that "the diet that is therapeutic for fully metabolically deranged cannot be unhealthy for the metabolically healthy." That's a fairly myopic viewpoint, as glucose control and all its hormonal sequellae have tremendous influence, well beyond AGEs and beta cells and amyloid deposition and such. Like every evolutionary scenario before us, the context of the *individual* matters. If someone has been gifted a bombproof (i.e. highly adaptive) pancreas, was not (epigenetically) wired to be intolerant to glucose, and does glycolytic activity on a regular basis, I'd posit that the *only* healthy option for him/her is the inclusion of some carbohydrate (from vegetables, fruit, and perhaps some "safe starches" if he/she is so inclined). In the absence of dietary carbohydrate, this person falls well outside Rosedale's statement in that they will actually be harmed by the inadequate intake of CHO (in my experience and opinion). What folks (like Rosedale or Taubes) that overstate or extrapolate their Explanation of Everything miss is that making observations about mathematical averages leaves out a whole lot of people. Context matters, and we do many people a great disservice by lumping them all into the great (and varied!) soup of humanity.

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Emily Deans, M.D.: I'm a psychiatrist in Massachusetts searching for evolutionary solutions to the general and mental health problems of the 21st century. Disclaimer: This information is for educational purposes only, and is in no way intended to be personal medical advice. Please ask your physician about any health guidelines seen in this blog, as everyone is different in his or her medical needs.